Efficient synthesis of 2-mono- and 2,5-disubstituted furans via the CuI-catalyzed cycloisomerization of alkynyl ketonest

Article abstract of DOI:10.1021/jo010832v

A mild, general, and efficient method for the synthesis of 2-monosubstituted and 2,5-disubstituted furans via the CuI-catalyzed cycloisomerization of alkynyl ketones was developed. It was demonstrated that furans containing both acid- and base-labile groups could be easily synthesized using this methodology. A plausible mechanism for this transformation is proposed.

Full text of DOI:10.1021/jo010832v

J . Org. Chem. 2002, 67, 95-98
95
Efficien t Syn th esis of 2-Mon o- a n d 2,5-Disu bstitu ted F u r a n s via
th e Cu I-Ca ta lyzed Cycloisom er iza tion of Alk yn yl Keton es†
Alexander V. Kel’in and Vladimir Gevorgyan*
Department of Chemistry, University of Illinois at Chicago, 845 West Taylor Street,
Chicago, Illinois 60607-7061
vlad@uic.edu
Received August 16, 2001
A mild, general, and efficient method for the synthesis of 2-monosubstituted and 2,5-disubstituted
furans via the CuI-catalyzed cycloisomerization of alkynyl ketones was developed. It was
demonstrated that furans containing both acid- and base-labile groups could be easily synthesized
using this methodology. A plausible mechanism for this transformation is proposed.
Furan is a very important heterocyclic unit broadly
found in natural1,2 and biologically important3 molecules
and frequently used as building block in material science4
and in organic synthesis.1a,5 Two general approaches are
commonly used for the preparation of substituted
furans: the first, functionalization of existing furan-
containing precursors by introduction of new substi-
tuents,1a,b and the second, formation of a new furan ring
by cyclization of acyclic substrates.1 The methods based
on functionalization of preexisting furan precursors are
not general. Thus, derivatization of furans via an elec-
trophilic substitution motif is restricted due to the low
stability of furans under strongly acidic conditions,1a,6
whereas protocols involving metalation of furan deriva-
tives followed by trapping of the furyl anion with
electrophiles1a,b are limited to base-stable furan sub-
strates and, in the case of alkylation, to primary elec-
trophiles only. Among cyclization approaches, the clas-
sical acid-catalyzed cyclocondensation of 1,4-dicarbonyl
compounds1a or related precursors2c still remains the
most powerful method for the construction of a substi-
tuted furan ring. Here again, some limitations may arise
in the case of acid-sensitive substrates. Recently, signifi-
cant attention has been paid to the development of
catalytic approaches, aiming at cycloisomerization of
unsaturated acyclic precursors into furans, which can
proceed under rather mild or neutral conditions.1-4,7-9 It
was reported that rhodium,7a silver,2a,b,7b and palladium7c
assist efficient cycloisomerization of allenyl ketones into
furans.9 A few scattered reports describing the palladium-
catalyzed cycloisomerization of the readily available,
stable, and thus synthetically most attractive alkynyl
ketones into furans are presented in the literature.10
However, the reported methods are limited mostly to the
synthesis of the aryl- or hetaryl-substituted furans and
allows for the preparation of the furan derivatives either
in moderate yields10a,c or accompanied with a trace to
notable amounts of dimeric products.10b Herein we wish
to disclose that various alkynyl ketones can be efficiently
and selectively converted into the corresponding furans
in the presence of catalytic amounts of CuI.
We have recently reported that alkynyl imines 1
undergo smooth transformation to pyrroles 2 in a Et3N-
DMA system (DMA ) N,N-dimethylacetamide) in the
presence of Cu(I) salts (eq 1).11
Encouraged by the successful transformation 1 f 2,
we tested this cycloisomerization protocol for the syn-
thesis of furans. It was found that the above-mentioned
reaction conditions were efficient for the conversion of
† Dedicated to Professor Edmund Lukevics on the occasion of his
65th Birthday.
(1) For reviews, see: (a) Eberbach, W. Furan. In Houben-Weyl;
Thieme: Stuttgart, 1994; E6a, Tail I, p 16. (b) Hou, X. L.; Cheung, H.
Y.; Hon, T. Y.; Kwan, P. L.; Lo, T. H.; Tong, S. Y.; Wong, H. N. C.
Tetrahedron 1998, 54, 1955. (c) Gilchrist, T. L. J . Chem. Soc., Perkin
Trans. 1 1999, 2849.
(2) (a) Marshall, J . A.; Wang, X.-J . J . Org. Chem. 1992, 57, 3387.
(b) Marshall, J . A.; Wallace, E. M. J . Org. Chem. 1995, 60, 796. (c)
Mendez-Andino, J .; Paquette, L. A. Org. Lett. 2000, 2, 4095, and
references therein.
(3) See, for example: Brown, T. H.; Armitage, M. A.; Blakemore, R.
C.; Blurton, P.; Durant, G. J .; Ganellin, C. R.; Ife, R. G.; Parsons, M.
E.; Rawlings, D. A.; Slingsby, B. P. Eur. J . Med. Chem. 1990, 25, 217.
(4) Lee, C.-F; Yang, L.-M.; Hwu, T.-Y.; Feng, A.-S.; Tseng, J .-C; Luh,
T.-Y. J . Am. Chem. Soc. 2000, 122, 4992, and references therein.
(5) See, for example: Kobayashi, Y.; Nakao, M.; Biju Kumar, G.;
Kishihara, K. J . Org. Chem. 1998, 63, 7505.
(7) (a) Marshall, J . A.; Robinson, E. D. J . Org. Chem. 1990, 55, 3450.
(b) Marshall, J . A.; Bartley G. S. J . Org. Chem. 1994, 59, 7169. (c)
Hashmi, A. S. K.; Ruppert, T. L.; Knofel, T.; Bats, J . W. J . Org. Chem.
1997, 62, 7295.
(8) Several complex furan derivatives have also been prepared by
Ag(I)- or Pd(II)-catalyzed cycloisomerization of hydroxyenynes: (a)
Marshall, J . A.; Sehon, C. A. J . Org. Chem. 1995, 60, 5966. (b)
Marshall, J . A.; Sehon, C. A. Org. Synth., 1998, 76, 263. (c) Gabriele,
B.; Salerno, G.; Lauria, E. J . Org. Chem. 1999, 64, 7687. (d) Gabriele,
B.; Salerno, G.; De Pascali, F.; Costa, M.; Chiusoli, G. P. J . Org. Chem.
1999, 64, 7693. (e) For a cascade Pd-catalyzed cross-carbonylation of
aryl iodides with aryl-alkynones, see: Okuro, K.; Furuune, M.; Miura,
M.; Nomura, M. J . Org. Chem. 1992, 57, 4754.
(9) Some of the these methods were applied for the total syntheses
of complex natural molecules containing a furan ring.2a,b
(10) (a) Sheng, H.; Lin, S.; Huang, Y. Tetrahedron Lett. 1986, 27,
4893. (b) J eevandandam, A.; Narkunan, K.; Cartwright, C.; Ling, Y.-
C. Tetrahedron Lett. 1999, 40, 4841. (c) Matsuo, K.; Sakaguchi, Y.
Heterocycles, 1996, 43, 2553. (d) Trost, B. M.; Schmidt, T. J . Am. Chem.
Soc. 1988, 110, 2301.
(6) For electrophilic functionalization of furan derivatives under mild
two-phase conditions, see: Lukevics, E.; Ignatovich, L.; Goldberg, Y.;
Polyak, F.; Gaukhman, A.; Rozite, S.; Popelis, J . J . Organomet. Chem.
1988, 348, 11.
(11) Kel'in, A. V.; Sromek, A. W.; Gevorgyan, V. J . Am. Chem. Soc.
2001, 123, 2074.
10.1021/jo010832v CCC: $22.00 © 2002 American Chemical Society
Published on Web 11/22/2001

96 J . Org. Chem., Vol. 67, No. 1, 2002
Ta ble 1. Cu (I)-Ca ta lyzed Syn th esis of F u r a n s 4
Kel’in and Gevorgyan
a
The reactions were performed in 1 mmol scale in 7:1 solution of DMA-Et3N (0.4 M) in the presence of 5 mol % of CuI, unless otherwise
specified. Isolated yield. c The reaction was carried out in the presence of 10 mol % of CuI. A catalytic amount of triethylamine (10 mol
b
d
%) was used; low yields of 4b were obtained in the presence of excess triethylamine.
alkynyl ketones 3a -j into the corresponding furans 4a -
j, as well (eq 2). In general, formation of furans 4 from
stituted furans 4c-j in good to excellent yields (Table 1,
entries 3-10). Noticeably, this method allowed for easy
introduction of various functional groups, such as an
alkenyl (4e), alkoxy (4g,i), and bulky t-Bu-group (4i)
directly into the furan ring. A remote ester group (4f), a
THP-protected alcohol (4h ,j), as well as an unprotected
hydroxyl group (4h ) have also been tolerated under these
reaction conditions (Table 1).
alkynyl ketones 3 (eq 2) appeared to be much easier than
the analogous transformation 1 to 2 (eq 1): most of the
reactions were completed in the presence of 5 mol % of
CuI, whereas 30-50 mol % of copper was needed for the
formation of pyrroles 2 (eq 1).11 Thus, cycloisomerization
of 1-phenylbut-2-yn-1-one (3a ) in the presence of 5 mol
% of CuI and excess triethylamine produced monosub-
stituted phenyl furan 4a in 85% yield (Table 1). Forma-
tion of the monoalkylated furan 4b, however, proceeded
less smoothly: this compound was obtained in 63% yield
only at a higher reaction temperature (130 °C) and in
the presence of a catalytic amount (10%) of triethylamine.
Cycloisomerization of alkynyl ketones 3c-j proceeded
with no complications, affording a variety of 2,5-disub-
We believe that the mechanism of the observed cycloi-
somerization of alkenyl ketones 3 into furans 4 (eq 2) is
closely related to the previously proposed mechanism for
the formation of pyrroles 2 from alkynyl imines 1 (eq 1).11
First triethylamine-Cu(I)-catalyzed isomerization of alky-
nyl ketone 3 leads to the formation of allenyl ketone 5
(Scheme 1). Coordination of copper to the terminal double
bond of allene (intermediate 6) makes it more electro-
philic and thus undergoes subsequent intramolecular
nucleophilic attack by an oxygen lone pair to produce the
zwitterionic intermediate 7. The latter isomerizes via a
deprotonation-protonation sequence12 into its more stable
isomer 8, which finally transforms into furan 4. The
intermediates 6 and 7 are structurally close to those

Efficient Synthesis of Furans via Cycloisomerization
J . Org. Chem., Vol. 67, No. 1, 2002 97
Sch em e 1
Exp er im en ta l Section
In str u m en ta tion . NMR spectra were recorded on Bruker
Avance DPX-400 (400 MHz) and on Brucker Avance DRX-500
(500 MHz) instruments. GC-MS analyses were performed on
a Hewlett-Packard Model 6890 GC interfaced to a Hewlett-
Packard Model 5973 mass selective detector (15 m × 0.25 mm
capillary column, HP-5MS). Column chromatography was
carried out by employing Merck silica gel (40-63 µm) or
Aldrich aluminum oxide (activated, neutral, Brockmann I,
∼150 mesh). Analytical thin-layer chromatography (TLC) was
performed on 0.2 mm precoated silica gel plates (60 F254) and
neutral aluminum oxide plates (60 F254). Alkynes, acyl chlo-
rides, anhydrous solvents, and common reagents were pur-
chased from Aldrich and Acros Organics.
Ak yn yl k eton es 3a ,d ,e were prepared by the reaction of
the corresponding alkynyl zinc chloride with benzoyl chloride
or 3,3-dimethylacryloyl chloride in the presence of Pd(PPh3)4
(Negishi coupling) according to the known procedure.17a Spec-
tral characteristics of known ketones 3a ,d were in agreement
with the reported data for 3a 17a and 3d .18
3e: 1H NMR (400 MHz, CDCl3) δ 6.11 (quint, 1H, J ) 1.1
Hz), 2.34 (t, 2H, J ) 7.0 Hz), 2.18 (d, 3H, J ) 1.0 Hz), 1.89 (d,
3H, J ) 1.0 Hz), 1.52-1.56 (m, 2H), 1.38-1.43 (m, 2H), 0.90
(t, 3H, J ) 7.5 Hz); 13C NMR (100 MHz, CDCl3) δ 176.9, 157.3,
126.2, 92.7, 83.2, 29.8, 27.8, 22.0, 21.0, 18.7, 13.5; MS m/z
(relative intensity) 163 (M+ - 1, 4), 135 (M+ - Et, 40), 79 (100);
previously proposed for the Ag-assisted7b and the Pd-
catalyzed7c cyloisomerization of allenyl ketones. To gain
an additional support for the step 3 f 5, the allenyl
ketone 5a was synthesized by an independent method13
and subjected to the cycloisomerization reaction. As
expected, 5a appeared to be much more reactive com-
pared to its propargyl precursor 3a (Table 1, entry 1),
affording 2-phenylfuran 4a even at room-temperature
albeit in 33% yield (eq 3).14
C
11H16O.
2-Decyn -3-on e 3b was prepared by the reaction of propy-
nylzinc chloride with heptanoyl chloride according to the
known procedure.17a Spectral data were in agreement with
reported data.19
3-Decyn -2-on e 3c was prepared by the reaction of octy-
nyllithium with DMA according to the known procedure,17a
spectral data were in agreement with the reported data.20
Alk yn yl Keton es 3f-j: Gen er a l P r oced u r e. Alkynyl
ketones 3f-j were prepared by the reaction of the correspond-
ing alkynylliythiums with the appropriate electrophiles (for
the details, see Table 1). To a stirred solution of alkyne (5
mmol) in Et2O (10 mL) (for compounds 3f,h ,j) or a mixture of
Et2O (5 mL) and THF (5 mL) (for compounds 3g,i) at 0 °C
was added a 2.5 M solution of BuLi in hexane (2.2 mL, 5.5
mmol) dropwise. The mixture was stirred for 0.5 h at 0 °C and
then slowly added via cannula into a solution of the corre-
sponding electrophile in Et2O (10 mL) at -78 °C. The mixture
was allowed to warm to 0 °C (in the cases 3f-i) and quenched
under vigorous stirring. In the case of 3j, the mixture was kept
for 1 h at -40 °C and allowed to warm to -10 °C before
quenching. The organic layer was separated, washed with 5%
aqueous NaCl, and dried over Na2SO4. The mixture was
concentrated under reduced pressure, and the residue was
chromatographed over a column of silica gel with EtOAc-
hexane mixtures and for compound 3j using Et2O-benzene
(1:20) as an eluent.
As a working hypothesis, this result can be rationalized
in the following way. The Cu(I)-catalyzed and base-
assisted propargyl-allenyl isomerization 3 to 5 is the
slowest step of the sequence, which produces allenic
intermediate 5 in very low concentrations. Allenyl ketone
5, once formed, immediately undergoes fast sequential
transformation into the stable furan derivative 415 (Scheme
1).16
In conclusion, general and effective method for the
synthesis of 2-monosubstituted and 2,5-disubstituted
furans from easily available alkynyl ketones17 in the
presence of catalytic amounts of Cu(I) was developed. The
generality of the method was demonstrated in the ef-
ficient preparation of furans possessing different func-
tional groups, such as the sterically hindered t-Bu group,
alkene moiety, alkoxy group directly attached to the
furan ring, as well as a remote acid sensitive OTHP
group, a base/nucleophile sensitive ester group, and an
unprotected hydroxyl group.
3f: 1H NMR (400 MHz, CDCl3) δ 3.68 (s, 3H), 2.87 (t, 2H,
J ) 6.8 Hz), 2.63 (t, 2H, J ) 6.7 Hz), 2.36 (t, 2H, J ) 7.0 Hz),
1.53-1.57 (m, 2H), 1.41-1.45 (m, 2H), 0.91 (t, 3H, J ) 7.5
(17) For classical approaches toward alkynyl ketones, see: (a)
Brandsma, L. Preparative acetylenic chemistry; Elsevier: New York,
1988. For the synthesis of alkynyl ketones from alkynyllithiums and
esters in the presence of BF3·Et2O, see: (b) Yamaguchi, M.; Shibato,
K.; Fujiwara, S., Hirao, I. Synthesis 1986, 421. For the Cu(I)-catalyzed
synthesis of alkynyl ketones from alkynes and acyl chlorides, see: (c)
Ramachandran, P. V.; Teodorovic, A. V.; Rangaishenvi, M. V.; Brown,
H. C. J . Org. Chem. 1992, 57, 2379. (d) Ito, H.; Arimoto, K.; Sensui,
H.; Hosomi, A. Tetrahedron Lett. 1997, 38, 3977. (e) Sashida, H.
Synthesis 1998, 745. For Lewis acid assisted coupling of TMS-
acetylenes with acyl chlorides, see: (f) J ones, G. E.; Holmes, A. B.
Tetrahedron Lett. 1982, 23, 3203. (g) Robertson, J .; Burrows, J . N.
Synthesis, 1998, 63. (h) For the synthesis of alkynyl ketones from
alkynyllithiums and Weinreb amides, see ref 10d.
(12) According to the deuterium labeling study performed for the
cycloisomerization of allenyl imines, we ruled out possible involvement
of “clean” hydrogen shifts and proposed a deprotonation-protonation
sequence that resulted in a net migration of two hydrogens from the
propargylic position into the heterocyclic ring.11
(13) Nagao, Y.; Lee, W.-S.; Kim, K. Chem. Lett. 1994, 389.
(14) The reaction was carried out without triethylamine. Total
decomposition of 5a observed in the presence of triethylamine.
(15) Analogously, a catalytic amount of triethylamine was used to
increase the yield of 4b (Table 1, entry 2, note c). Most likely, an allenic
intermediate 5b (R1 ) H, R2 ) n-Hex) was produced in high concentra-
tion in the presence of excess triethylamine, which caused its rapid
decomposition under harsh reaction conditions.
(18) Kang, S.-K.; Lim, K.-H.; Ho, P.-S.; Kim, W.-Y. Synthesis 1997,
874.
(16) This presumption is in agreement with the fact that allenic
intermediate 5 has never been detected by GC-MS analyses of crude
reaction mixtures.
(19) Marshall, J . A.; Wang, X. J . Org. Chem. 1991, 56, 4913.
(20) Luo, F. -T.; Bajji, A. C.; J eevanandam, A. J . Org. Chem. 1999,
64, 1738.

98 J . Org. Chem., Vol. 67, No. 1, 2002
Ta ble 2. Exp er im en ta l Deta ils for th e Syn th esis of Alk yn yl Keton es 2f-j
Kel’in and Gevorgyan
product/
alkyne
electrophile (amount)
solution for quenching
yield (%)
1
2
3
4
5
1-hexyne
methyl 4-chloro-4-oxobutyrate
(10 mmol)
heptanoyl chloride
(10 mmol)
γ-butyrolactone
(6 mmol)
1% aq NH3 (35 mL)
3f/48
methylpropargyl ether
1% aq NH3 (35 mL)
3g/46
3h /65
3i/89
3j/60
4-tetrahydropyranyloxy-1-butyne
sat. aq NH4Cl(10 mL) + H2O(20 mL)
sat. aq NH4Cl (10 mL) + 1% aq NH3 (10 mL)
3-tetrahydropyranyloxy-1-propyne pivalic anhydride
(7.5 mmol)
5-phenyl-1-pentyne
methyl tetrahydropyranyloxyacetate sat. aq NH4Cl (10 mL) + H2O (20 mL) +
(7.5 mmol) AcOH (0.54 mL)
Hz); 13C NMR (100 MHz, CDCl3) δ 185.6, 172.6, 95.2, 80.4,
51.9, 40.0, 29.6, 27.8, 21.9, 18.6, 13.5; MS m/z (relative
intensity) 196 (M+, 0.5), 165 (M+ - OMe, 3), 109 (100);
4f: 1H NMR (400 MHz, CDCl3) δ 5.88 (d, 1H, J ) 2.8 Hz),
5.84 (d, 1H, J ) 2.8 Hz), 3.68 (s, 3H), 2.92 (t, 2H, J ) 7.3 Hz),
2.63 (t, 2H, J ) 7.0 Hz), 2.53 (t, 2H, J ) 7.5 Hz), 1.58-1.65
(m, 2H), 0.94 (t, 3H, J ) 7.3 Hz); 13C NMR (100 MHz, CDCl3)
δ 173.5, 155.5, 152.5, 106.0, 105.6, 52.0, 33.0, 30.4, 24.0, 21.8,
14.1; MS m/z (relative intensity) 196 (M+, 15), 167 (M+ - Et,
19), 123 (56), 107 (100). Anal. Calcd for C11H16O3: C, 67.31;
H, 8.22. Found: C, 67.40; H, 7.95.
4g: 1H NMR (400 MHz, CDCl3) δ 5.81 (dd, 1H, J 1 ) 2.4, J 2
) 0.9 Hz), 4.99 (d, 1H, J ) 3.0 Hz), 3.80 (s, 3H), 2.49 (t, 2H, J
) 7.9 Hz), 1.52-1.65 (m, 2H), 1.24-1.37 (m, 6H), 0.88 (t, 3H,
J ) 6.9 Hz); 13C NMR (126 MHz, CDCl3) δ 160.7, 146.8, 105.6,
79.6, 58.0, 32.0, 29.2, 28.4 (x2), 23.0, 14.5; MS m/z (relative
intensity) 182 (M+, 10), 111 (100); C11H18O2.
4h : 1H NMR (400 MHz, CDCl3) δ 6.19 (d, 1H, J ) 3.0 Hz),
5.92 (d, 1H, J ) 3.2 Hz), 4.68 (t, 1H, J ) 3.4 Hz), 4.58 (d, 1H,
J ) 12.8 Hz), 4.41 (d, 1H, J ) 12.8 Hz), 3.87 (t, 1H, J ) 7.4
Hz), 3.63 (t, 2H, J ) 6.4 Hz), 3.44-3.54 (m, 1H), 2.68 (t, 2H,
J ) 7.5 Hz), 2.22 (s, 1H), 1.74-1.92 (m, 3H), 1.62-1.74 (m,
1H), 1.38-1.62 (m, 4H); 13C NMR (100 MHz, CDCl3) δ 156.1,
149.9, 110.2, 105.7, 97.1, 62.0, 61.8, 60.7, 30.9, 30.3, 25.4, 24.4,
19.2; MS m/z (relative intensity) 156 (M+ - THP, 8), 138 (47),
55 (100); Anal. Calcd for C13H20O4: C, 64.96; H, 8.39. Found:
C, 65.15; H, 8.34.
4i: 1H NMR (400 MHz, CDCl3) δ 5.79 (d, 1H, J ) 3.0 Hz),
5.32 (t, 1H, J ) 2.8 Hz), 5.26 (d, 1H, J ) 3.3 Hz), 3.98 (td, 1H,
J 1 ) 13.9 Hz, J 2 ) 2.8 Hz), 3.63-3.66 (m, 1H), 1.90-2.07 (m,
2H), 1.62-1.90 (m, 4H), 1.24 (s, 9H); 13C NMR (100 MHz,
CDCl3) δ 157.2, 154.4, 102.4, 99.2, 84.2, 61.7, 32.3, 29.6, 28.9
(×3), 25.0, 18.0; MS m/z (relative intensity) 224 (M+, 0.5), 209
(M+ - Me, 1), 125 (22), 85 (100). Anal. Calcd for C13H20O3: C,
69.60; H, 8.99. Found: C, 69.55; H, 8.86.
4j: 1H NMR (400 MHz, CDCl3) δ 7.28-7.32 (m, 2H), 7.19-
7.23 (m, 3H), 6.23 (d, 1H, J ) 3.1 Hz), 5.94 (d, 1H, J ) 3.1
Hz), 4.74 (t, 1H, J ) 3.5 Hz), 4.66 (d, 1H, J ) 12.8 Hz), 4.49
(d, 1H, J ) 12.8 Hz), 3.94 (t, 1H, J ) 7.4 Hz), 3.52-3.62 (m,
1H), 2.91-3.04 (m, 4H), 1.82-1.95 (m, 1H), 1.70-1.82 (m, 1H),
1.49-1.70 (m, 4H); 13C NMR (100 MHz, CDCl3) δ 155.9, 150.0,
141.2, 128.4 (×4), 126.1, 110.2, 106.0, 97.1, 62.0, 60.7, 34.3,
30.4, 30.1, 25.5, 19.3; MS m/z (relative intensity) 286 (M+, 0.5),
184 (76), 141 (100). Anal. Calcd for C18H22O3: C, 75.48; H, 7.75.
Found: C, 75.23; H, 7.75.
Cycloisom er iza tion of Allen yl Keton e 5a in DMA in
th e P r esen ce of Cu I. The mixture of CuI (9.6 mg, 0.05 mmol),
ketone 5a 13 (163 mg, 1.1 mmol), and anhydrous DMA (2.5 mL)
was stirred under argon atmosphere at room temperature for
43 h and quenched as described above. Column chromatogra-
phy (silica gel pentane as an eluent) gave 54 mg (33%) of
2-phenylfuran.21
C
11H16O3.
3g: (46%): 1H NMR (400 MHz, CDCl3) δ 4.26 (s, 2H), 3.41
(s, 3H), 2.56 (t, 2H, J ) 7.3 Hz), 1.64-1.68 (m, 2H), 1.27-1.33
(m, 6H), 0.88 (t, 3H, J ) 6.8 Hz); 13C NMR (100 MHz, CDCl3)
δ 187.6, 87.3, 85.4, 59.6, 58.0, 45.4, 31.5, 28.6, 23.9, 22.4, 14.0;
MS m/z (relative intensity) 182 (M+, 0.5), 152 (M+ - Et, 2),
112 (67), 97 (100); C11H18O2.
3h : 1H NMR (500 MHz, CDCl3) δ 4.64 (s, 1H), 3.85-3.95
(m, 2H), 3.54-3.64 (m, 3H), 3.44-3.54 (m, 1H), 2.62-2.77 (m,
4H), 2.26 (s broad, 1H), 1.88-1.92 (m, 2H), 1.74-1.87 (m, 1H),
1.64-1.74 (m, 1H), 1.44-1.59 (m, 4H); 13C NMR (100 MHz,
CDCl3) δ 188.4, 99.3, 91.9, 81.6, 65.0, 62.7, 62.0, 42.5, 30.9,
27.2, 25.7, 20.9, 19.7; C13H20O4.
3i: 1H NMR (400 MHz, CDCl3) δ 4.80 (t, 1H, J ) 3.3 Hz),
4.41 (s, 2H), 3.79-3.85 (m, 1H), 3.49-3.59 (m, 1H), 1.64-1.85
(m, 2H), 1.49-1.64 (m, 4H), 1.15 (s, 9H); 13C NMR (100 MHz,
CDCl3) δ 193.6, 97.0, 89.5, 82.9, 62.0, 53.8, 44.6, 30.0, 25.9
(×3), 25.2, 18.8; MS m/z (relative intensity) 167 (M+ - t-Bu,
0.5), 124 (6), 85 (32), 57 (100); C13H20O3.
3j: 1H NMR (400 MHz, CDCl3) δ 7.26-7.31 (m, 2H), 7.17-
7.22 (m, 3H), 4.72 (t, 1H, J ) 3.4 Hz), 4.34 (s, 2H), 3.85 (t, 1H,
J ) 9.2 Hz), 3.51-3.54 (m, 1H), 2.74 (t, 2H, J ) 7.4 Hz), 2.38
(t, 2H, J ) 7.0 Hz), 1.79-1.95 (m, 3H), 1.69-1.79 (m, 2H),
1.46-1.69 (m, 3H); 13C NMR (100 MHz, CDCl3) δ 184.9, 140.7,
128.5 (×4), 126.2, 98.3, 96.7, 79.1, 72.5, 62.0, 34.6, 30.1, 29.1,
25.3, 18.9, 18.4; MS m/z (relative intensity) 228 (1.5), 202 (M+
- THP, 4), 171 (24), 128 (55), 104 (83), 85 (100); C18H22O3.
F u r a n s 4a -j: Gen er a l P r oced u r e. A mixture of propynyl
ketone 3a -j (1 mmol), CuI (9.6 mg, 0.05 mmol) (in cases of
3b,e, 19 mg, 0.1 mmol), anhydrous DMA (2.2 mL) (in the case
of 3b, 2.5 mL), and Et3N (0.3 mL) (in the case of 3b, catalytic
amount, i.e., 14 µL, 0.1 mmol) was stirred in a Wheaton
microreactor (3 mL) under argon atmosphere (at the temper-
ature given in Table 1) until the reaction was complete
(monitored by GC-MS and TLC). The mixture was cooled,
diluted (water, 15 mL), and extracted (pentane for volatile
products 4a -c,e, hexane for nonpolar products 4d ,f,g,i,j, ether
for polar compound 4h , 3 × 5 mL). Combined organic extracts
were filtered (anhydrous Na2CO3), concentrated under reduced
pressure, and chromatographed over a short column (silica gel;
pentane as eluent for 4a -c,e, hexane for 4d , and mixtures
EtOAc-hexane for 4f,h -j). Compound 4g appeared to be
hydrolytically unstable on silica gel and was purified over a
short column of Al2O3 with hexane as the eluent. Spectroscopic
data for known products (4a ,21 4b,22 4c,20 4d 23) were in
agreement with the reported data.
4e: 1H NMR (400 MHz, CDCl3) δ 6.05 (d, 1H, J ) 3.1 Hz),
6.02 (s, 1H), 5.97 (d, 1H, J ) 3.2 Hz), 2.59 (t, 2H, J ) 7.5 Hz),
1.98 (s, 3H), 1.89 (s, 3H), 1.67 (sext., 2H, J ) 7.5 Hz), 0.97 (t,
3H, J ) 7.2 Hz); 13C NMR (100 MHz, CDCl3) δ 154.4, 152.0,
133.5, 114.5, 107.7, 106.2, 30.2, 26.9, 21.4, 20.0, 13.8; MS m/z
(relative intensity) 164 (M+, 23), 135 (M+ - Et, 100); C11H16O.
Ack n ow led gm en t. The support provided by the
National Science Foundation (CHE 0096889) is grate-
fully acknowledged.
Su p p or t in g In for m a t ion Ava ila b le: 1H and 13C NMR
charts for compounds 4e and 4g. This material is available
free of charge via Internet at http://pubs.acs.org
(21) Pelter, A.; Rowlands, M.; Clements, G. Synthesis 1987, 51.
(22) Sheu, J .-H.; Yen, C.-F.; Huang, H.-C.; Hong, Y.-L. V. J . Org.
Chem. 1989, 54, 5126.
(23) Padwa, A.; Kassir, J . M.; Xu, S. L. J . Org. Chem. 1997, 62, 1642.
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